US20110092844A1 - Micro-insult test and use therefor - Google Patents

Micro-insult test and use therefor Download PDF

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Publication number
US20110092844A1
US20110092844A1 US12/580,819 US58081909A US2011092844A1 US 20110092844 A1 US20110092844 A1 US 20110092844A1 US 58081909 A US58081909 A US 58081909A US 2011092844 A1 US2011092844 A1 US 2011092844A1
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United States
Prior art keywords
micro
area
microscopy
insult
skin
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
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US12/580,819
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English (en)
Inventor
Paulo R. Bargo
Nikiforos Kollias
Inseok Seo
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Johnson and Johnson Consumer Inc
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Johnson and Johnson Consumer Companies LLC
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Filing date
Publication date
Application filed by Johnson and Johnson Consumer Companies LLC filed Critical Johnson and Johnson Consumer Companies LLC
Priority to US12/580,819 priority Critical patent/US20110092844A1/en
Assigned to JOHNSON & JOHNSON CONSUMER COMPANIES, INC. reassignment JOHNSON & JOHNSON CONSUMER COMPANIES, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BARGO, PAULO R, KOLLIAS, NIKIFOROS, SEO, INSEOK
Priority to EP10251801A priority patent/EP2324766A3/de
Priority to CA2717710A priority patent/CA2717710A1/en
Priority to KR1020100101115A priority patent/KR20110042022A/ko
Priority to CN201010522086.6A priority patent/CN102038492A/zh
Priority to BRPI1003932A priority patent/BRPI1003932A2/pt
Publication of US20110092844A1 publication Critical patent/US20110092844A1/en
Abandoned legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0068—Confocal scanning
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/411—Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/445—Evaluating skin irritation or skin trauma, e.g. rash, eczema, wound, bed sore

Definitions

  • the present invention relates to a method for testing human skin and other biological tissues, and the use thereof for testing the effects of ingredients and compositions on such tissues in vivo.
  • Some microscopic techniques have been developed for the treatment of skin aging, i.e., reduction of wrinkles, to minimize the harm to epidermis and reduce the risk of side effects, complications, and downtime.
  • Such techniques involve inducing an array of microscopic wounds on the skin surface that are rapidly re-epithelialized by the surrounding, undamaged tissue, sparing the epidermis.
  • a laser with infrared wavelength is often used, and the radiation is absorbed by aqueous components inside the tissue with limited and controlled areas of photocoagulation that stimulate a therapeutic response deep in the dermis. This leads to increased production of neo-collagen and improvement in skin tone and texture.
  • the present invention is directed to a method for testing human skin, which comprises causing at least one micro-insult to an area of the human skin; and monitoring the area using an imaging technique.
  • the present invention provides a method for determining the effects of a topically applied composition to human skin, which comprises in sequence applying the composition to an area of the human skin; causing at least one micro-insult to the area; and monitoring the area using an imaging technique.
  • the present invention provides a method for determining the effects of a topically applied composition to human skin, which comprises in sequence causing at least one micro-insult to an area of the human skin; applying the composition to the area; and monitoring the area using an imagining technique.
  • FIGS. 1A and 1B are cross-polarized images of micro-wounds described in Example 1.
  • FIGS. 2A , 2 B, 2 C, 2 D and 2 E are confocal microscope images of the micro-wounds described in Example 1 after 30 minutes.
  • FIG. 2F shows the intensity depth profile from three different regions of one confocal microscopy image stack for a subject: treated area, surrounding area and untreated area, as described in Example 1.
  • FIGS. 3A , 3 B, 3 C and 3 D are cross-polarized images of microscopic wounds described in Example 1 acquired with video microscopy at 30 minutes, 2 days, 4 days and 23 days after treatment.
  • FIG. 4 depicts the confocal microscopic images and depth intensity profiles for the microscopic wounds shown in FIGS. 3A , 3 B, 3 C and 3 D.
  • FIGS. 5A , 5 B and 5 C are normalized depth intensity profiles of a 25 year old subject, a 53 year old subject and a 30 year old subject at different time points after treatment, as described in Example 1.
  • FIGS. 7A and 7B are cross-polarized images of UV irradiated sites through optical fibers and circular slits, as described in Example 2.
  • FIG. 8 depicts cross-polarized microscopic (20 ⁇ -400 ⁇ magnification) images taken at different days after UV irradiation of a subject, as described in Example 2.
  • FIG. 9 shows cross-polarized microscopic images taken at days 0, 1 6 and 10 says after UV irradiation of a subject, as described in Example 2.
  • FIG. 10B shows cross-polarized images of a UV phototest performed performed using the method of the invention and a standard COLIPA-recommended method application of a sunscreen, as described in Example 3.
  • the methods and systems described herein may also be used for the testing of other human and animal biological tissues, such as hair, lips, oral mucosa, and internal organs (esophagus, arteries, intestines, liver, etc.), for example optionally with the use of optical fibers or laparoscopic/endoscopic techniques.
  • the invention provides a method for testing human skin, which comprises causing at least one micro-insult to an area of the human skin; and monitoring the area using an imaging technique.
  • the method may be used for evaluating the effects of ingredients or compositions on human skin.
  • the method may be used for allergy testing or cosmetic product/drug efficacy testing.
  • the effects of anti-acne products, anti-aging products, sunscreen products, or wound healing products, or the like, for instance, may be tested according to the invention.
  • the invention also provides a method for determining the effects of a topically applied composition to human skin, which comprises applying the composition to an area of the human skin; causing at least one micro-insult to the area; and monitoring the area using an imaging technique.
  • Application of the composition may be done before or after the micro-insult is applied to the skin.
  • the shape of the micro-insults is not critical. They are preferably disconnected and spaced far enough apart so that each can be monitored individually. Spacing between the micro-insults may be at least about 10 um, for example about 10 um to about 1,000 um, but may also be less, i.e., less than about 10 um, if interactions between or among a plurality of micro-insults are analyzed. Spacing may be on a regular or irregular basis. Preferably, the spacing is on a regular basis, that is, at fixed and uniform intervals.
  • the micro-insults are monitored using an imaging technique.
  • the imaging technique may be a microscopic or macroscopic imaging technique.
  • the imaging technique is used to evaluate the effects of the micro-insult on changes in the morphology or physiology of the tissue being tested.
  • Monitoring may comprise a single analysis of an area of tissue using a single image, or multiple analyses of an area of tissue using multiple images generated using one imaging technique or more than one imaging technique. For example, monitoring may comprise the analysis or comparison of multiple, sequential images of an area of tissue collected over predetermined time intervals.
  • Suitable imaging techniques include, but are not limited to confocal microscopy, digital imaging, fluorescence microscopy, optical coherence tomography (OCT), two-photon fluorescence microscopy, second harmonic generation microscopy, coherent anti-Stokes Raman scattering (CARS) microscopy, and spectral imaging.
  • the imaging technique is a microscopic imaging technique.
  • the method of the present invention is advantageous because it is predictive of the effects of macro-insults to the skin (or other tissues), but with minimum adverse effect or damage to the skin due to the extremely small size of the injury.
  • the method provides quick recovery, low discomfort to the test subject, and may be used on different parts of the body, including the sensitive areas of the face and lips, or on internal organs.
  • a particularly suitable use for the present methods is for assessing the efficacy of skin care products.
  • one area of skin may be treated with a sunscreen and another area of skin of the same subject may be untreated. Both areas of skin may then exposed to micro-insults in the form of UV irradiation. Following this, images of both areas may be obtained using an imaging technique and then compared to determine the effect of the sunscreen.
  • the methods of the present invention may also be useful for allergy testing.
  • small capillary tubes small amounts of allergens may be applied to an area of the skin to create micro-insults thereon.
  • the skin may be monitored using a microscopic imaging technique for signs of an allergic reaction, such as swelling, erythema and the like.
  • the dynamic response of the micro-wound healing process was monitored at 30 minutes after treatment, 2 days, 4 days, and 3 weeks after the treatment in vivo using multi-modal microscopic and macroscopic imaging techniques, including video microscopy (KH-300, Hirox, Japan) and reflectance-mode laser scanning confocal microscopy (Vivascan 1500, Lucid, Rochester, N.Y.) with an operating power of less than 20 mW and the lateral resolution of ⁇ 1 micron and the axial resolution of ⁇ 5 microns at 785 nm.
  • video microscopy KH-300, Hirox, Japan
  • reflectance-mode laser scanning confocal microscopy Vivascan 1500, Lucid, Rochester, N.Y.
  • FIGS. 1A and 1B show a cross-polarized image using video microscope and the corresponding reflectance mode confocal microscopic image for one of the subjects.
  • Cross-polarization effectively removed the surface glare and highlighted sub-surface features of pigmentation and vasculature.
  • the micro-wounds appeared as a line of dark brown spots, while their corresponding confocal microscopic image appeared to be bright in the wounded area at around 80 microns below the skin surface, indicating stronger scattering in the micro-wound area.
  • FIGS. 2A , 2 B, 2 C, 2 D, 2 D and 2 E depict the confocal microscopic images from the volar forearm of a 27-year-old female Caucasian at around 30 minutes after the laser treatment (60 mJ per micro-wound).
  • FIG. 2F shows the corresponding depth intensity profile. At the top 10-15 microns below the skin surface, there was only a slight increase in reflection in the treated microthermal zone compared to the surrounding area and normal area, indicating the minimal damage to the skin at the surface. At 20 to 50 microns below the skin surface, there was a significant increase in reflection within the treated micro-zone. The increased intensity within the micro-zone may have been due to swelling, causing the refractive index mismatch from the superficial layer.
  • FIG. 4 shows the confocal microscopic images and corresponding depth intensity profiles for the same subject at 30 minutes, 2 days, 4 days and 23 days after treatment.
  • FIG. 4( a ) shows the representative depth intensity profile of a treated micro-wound, the surrounding collateral damage zone and normal area at the specified time points. The profile from normal skin retained similar patterns over time. Compared to the normal area, the depth intensity profile of the treated micro-wound showed progressive increase in intensity from 20 to 100 microns below the surface until 4 days after treatment, and then returned to the similar pattern of normal skin after 3 weeks post-treatment. The surrounding collateral damaged zone showed little change compared to normal skin 30 minutes after treatment, then showed a significant increase in intensity after 2 days and 4 days, and then returned to normal after 23 days.
  • the depth intensity profiles also indicated that there was minimal change in the superficial skin within the top 20 microns of the skin surface, confirming the clinical observation of minimal harm to the superficial epidermis.
  • the depth intensity profiles provided a quantitative measure of the associated cellular structure changes.
  • FIGS. 5A. 5B , and 5 D show the normalized depth intensity profiles of subjects of different ages at different time points after treatment (60 mJ per micro-wound).
  • the normalized depth intensity profiles showed a peak and the peak position first shifted to the deeper depth and then returned to shallower depth. The transition time point when the peak position shifted back to the shallower depth depended on age.
  • a normalized depth intensity profile may be used as a quantitative method to evaluate the wound-healing rate at a microscopic cellular level.
  • the optical fibers were securely placed onto the skin throughout the experiment so that the irradiation was limited to the diameter of the fiber/slit. Double stick tape was used to attach the fibers to the skin. Multi-modal microscopic and macroscopic imaging techniques such as cross-polarized digital imaging, UV-excited fluorescence imaging, spectral imaging, video microscopy (KH-300, Hirox, Japan) and reflectance-mode laser scanning confocal microscopy (Vivascan 1500, Lucid, Rochester, N.Y.), were used to evaluate the progress of healing after irradiation. In order to monitor the micro-insults, the optical probes/slits were arranged in a line.
  • FIG. 7B shows the erythema level for irradiations with the 200 um optical fiber probe (top) and the 2 mm diameter circular optical fiber probe (bottom).
  • the doses for the 200 um optical fiber probe were 60, 120, 240 and 400 mJ/cm 2 from left to right, and 120 and 240 mJ/cm 2 for the 2 mm diameter circular optical fiber probe.
  • FIG. 8 Microscopic imaging (HiScope) taken at different days after skin irradiation was used to track the development of the micro-injuries over an extended period of time at several optical magnifications and is shown in FIG. 8 .
  • FIG. 9 shows similar images taken at sequential timepoints after irradiation. The different aspects of the micro-injuries such as erythema immediately and at 24 hours and pigmentation at 6 and 11 days post irradiation are depicted.
  • the performance of a sunscreen with sun protection factor SPF 48 was evaluated in vivo according to the invention as follows.
  • a solar simulator of the same type described in Example 2 was used to apply microscopic insults of UV radiation in increments of 25%.
  • the skin was tested without sunscreen to determine the MED for the subject.
  • FIG. 10A shows the results. This test was done with both a micro-injury fiber and a regular phototest fiber having an 8 mm diameter for comparison as recommended by the COLIPA standard. Doses of 15.5, 12.4, 9.9, 7.9, 6.3, and 5.1 mJ/cm 2 for sites 1 - 6 , respectively, were applied.
  • the MED was determined to be 9.9 mJ/cm 2 (site 3 ).
  • the sunscreen was then uniformly applied (2 ml/mm 2 ) and the skin was irradiated with doses 470, 381, 304.8, mJ/cm 2 for sites 1 - 3 , respectively ( FIG. 10B ).
  • Sites “ 1 a ,” “ 2 a ,” and “ 3 a ” were irradiated using an 8 mm diameter fiber and sites “ 1 b ,” “ 2 b ” and “ 3 b ” were irradiated using a micro-injury fiber.
  • the MED with sunscreen was determined to be 470 mJ/cm 2 (site 1 ).
  • method of the invention may be used to predict the in vivo SPF value of a sunscreen composition accurately.
US12/580,819 2009-10-16 2009-10-16 Micro-insult test and use therefor Abandoned US20110092844A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US12/580,819 US20110092844A1 (en) 2009-10-16 2009-10-16 Micro-insult test and use therefor
EP10251801A EP2324766A3 (de) 2009-10-16 2010-10-15 Mikro-Insult-Test und Verwendung dafür
CA2717710A CA2717710A1 (en) 2009-10-16 2010-10-15 Micro-insult test and use therefor
KR1020100101115A KR20110042022A (ko) 2009-10-16 2010-10-15 미세 상해 시험 및 그의 용도
CN201010522086.6A CN102038492A (zh) 2009-10-16 2010-10-18 微创伤测试及其用途
BRPI1003932A BRPI1003932A2 (pt) 2009-10-16 2010-10-18 teste de microlesão e uso do mesmo

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US12/580,819 US20110092844A1 (en) 2009-10-16 2009-10-16 Micro-insult test and use therefor

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US (1) US20110092844A1 (de)
EP (1) EP2324766A3 (de)
KR (1) KR20110042022A (de)
CN (1) CN102038492A (de)
BR (1) BRPI1003932A2 (de)
CA (1) CA2717710A1 (de)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160095592A1 (en) * 2013-05-03 2016-04-07 Cytrellis Biosystems, Inc. Microclosures and related methods for skin treatment
US10251792B2 (en) 2013-02-20 2019-04-09 Cytrellis Biosystems, Inc. Methods and devices for skin tightening
US10555754B2 (en) 2013-08-09 2020-02-11 Cytrellis Biosystems, Inc. Methods and apparatuses for skin treatment using non-thermal tissue ablation
US10953143B2 (en) 2013-12-19 2021-03-23 Cytrellis Biosystems, Inc. Methods and devices for manipulating subdermal fat
US11166743B2 (en) 2016-03-29 2021-11-09 Cytrellis Biosystems, Inc. Devices and methods for cosmetic skin resurfacing
US11324534B2 (en) 2014-11-14 2022-05-10 Cytrellis Biosystems, Inc. Devices and methods for ablation of the skin
US11464954B2 (en) 2016-09-21 2022-10-11 Cytrellis Biosystems, Inc. Devices and methods for cosmetic skin resurfacing

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109770853B (zh) * 2019-01-30 2022-01-14 上海师范大学 一种斑马鱼伤口检测方法

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US6663658B1 (en) * 1999-04-27 2003-12-16 The General Hospital Corporation Phototherapy method for treatment of acne
US6703490B1 (en) * 1995-10-17 2004-03-09 Coletica Amphiphilic complexes, method for their preparation and compositions containing them
US20060182323A1 (en) * 2005-02-17 2006-08-17 Nikiforos Kollias Device and method for demonstrating and quantifying skin texture
US20080214952A1 (en) * 2005-07-11 2008-09-04 Jose Mir Replaceable Cartridge for Allergy Testing System
US20080221405A1 (en) * 2007-03-08 2008-09-11 The Procter & Gamble Company Method for assessing subsurface irritation of skin

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DE10203377A1 (de) * 2002-01-29 2003-07-31 Zn Vision Technologies Ag Verfahren zur bildgestützten Auswertung von Allergiefaktoren

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Publication number Priority date Publication date Assignee Title
US6703490B1 (en) * 1995-10-17 2004-03-09 Coletica Amphiphilic complexes, method for their preparation and compositions containing them
US6663658B1 (en) * 1999-04-27 2003-12-16 The General Hospital Corporation Phototherapy method for treatment of acne
US20060182323A1 (en) * 2005-02-17 2006-08-17 Nikiforos Kollias Device and method for demonstrating and quantifying skin texture
US20080214952A1 (en) * 2005-07-11 2008-09-04 Jose Mir Replaceable Cartridge for Allergy Testing System
US20080221405A1 (en) * 2007-03-08 2008-09-11 The Procter & Gamble Company Method for assessing subsurface irritation of skin

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10251792B2 (en) 2013-02-20 2019-04-09 Cytrellis Biosystems, Inc. Methods and devices for skin tightening
US10543127B2 (en) 2013-02-20 2020-01-28 Cytrellis Biosystems, Inc. Methods and devices for skin tightening
US11534344B2 (en) 2013-02-20 2022-12-27 Cytrellis Biosystems, Inc. Methods and devices for skin tightening
US20160095592A1 (en) * 2013-05-03 2016-04-07 Cytrellis Biosystems, Inc. Microclosures and related methods for skin treatment
US10555754B2 (en) 2013-08-09 2020-02-11 Cytrellis Biosystems, Inc. Methods and apparatuses for skin treatment using non-thermal tissue ablation
US10953143B2 (en) 2013-12-19 2021-03-23 Cytrellis Biosystems, Inc. Methods and devices for manipulating subdermal fat
US11324534B2 (en) 2014-11-14 2022-05-10 Cytrellis Biosystems, Inc. Devices and methods for ablation of the skin
US11896261B2 (en) 2014-11-14 2024-02-13 Cytrellis Biosystems, Inc. Devices and methods for ablation of the skin
US11166743B2 (en) 2016-03-29 2021-11-09 Cytrellis Biosystems, Inc. Devices and methods for cosmetic skin resurfacing
US11464954B2 (en) 2016-09-21 2022-10-11 Cytrellis Biosystems, Inc. Devices and methods for cosmetic skin resurfacing

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Publication number Publication date
BRPI1003932A2 (pt) 2015-10-27
CA2717710A1 (en) 2011-04-16
KR20110042022A (ko) 2011-04-22
CN102038492A (zh) 2011-05-04
EP2324766A3 (de) 2012-06-20
EP2324766A2 (de) 2011-05-25

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